Stimulation of 42/44 kDa mitogen-activated protein kinases by arginine vasopressin in rat cardiomyocytes.
Vasoconstrictors, such as angiotensin II (Ang II), are involved in the regulatory mechanisms of post myocardial infarction (MI) hypertrophy. Arginine vasopressin (AVP), may be another vasoconstrictor that influences the mechanisms that lead to post MI hypertrophy. In these studies we investigated the possible activation of the 42/44 kDa mitogen-activated protein kinases (MAPKs), also referred as extracellular signal regulated kinases (ERKs), in cultured cardiomyocytes. Treatment of rat cardiomyocytes with AVP, Ang II and phorbol 12-myristate 13-acetate (PMA) increases the activation of ERKs. The activity of the 42/44 kDa MAPKs was tested using the phosphorylation of: (1) EGF receptor peptide (EGFR-P); (2) myelin basic protein (MBP) immobilized in poly acrylamide gels; and (3) T183 and Y185 residues of these proteins. The activity of the MAPKs, induced by AVP or PMA was inhibited by downregulation of protein kinase C (PKC), by the tyrosine kinase inhibitor genistein and by MAPK kinase (MEK) inhibitor, PD98059. In addition, the AVP-induced stimulation of MAPKs was shown to be mediated through a V1 receptor. We suggest that AVP activates the 42/44kDa MAPKs through a signal transduction pathway that involves stimulation of AVP-V1 receptor, tyrosine kinase, PKC and MEK. These results suggest that AVP may be involved in ERKs dependent regulatory functions of cardiomyocytes growth.
Aharonovitz
O
O
Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Aboulafia-Etzion
S
S
Leor
J
J
Battler
A
A
Granot
Y
Y
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017483:Receptors, Vasopressin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D004791:Enzyme Inhibitors; D004676:Myelin Basic Protein; D047428:Protein Kinase Inhibitors; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D013912:Threonine; D014443:Tyrosine; D011494:Protein Kinases; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate